Anti-inflammatory properties of mutolide isolated from the fungus Lepidosphaeria species (PM0651419) View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Meet Shah, Sunil Kumar Deshmukh, Shilpa A. Verekar, Akash Gohil, Abhijeet S. Kate, V. Rekha, Asha Kulkarni-Almeida

ABSTRACT

Mutolide an anti-inflammatory compound was isolated from the coprophilous fungus Lepidosphaeria sp. (PM0651419). The compound mitigated LPS-induced secretion of pro-inflammatory cytokines TNF-α and IL-6 from THP-1 cells as well as human peripheral blood mononuclear cells (hPBMCs). Mutolide also inhibited secretion of another pro-inflammatory cytokine IL-17 from anti-hCD3/anti-hCD28 stimulated hPBMCs. NF-κB is the major transcription factor involved in the secretion of pro-inflammatory cytokines including IL-17. Mechanistic evaluations revealed that mutolide inhibited induced NF-κB activation and translocation from cytoplasm into the nucleus. However, mutolide did not significantly affect activity of p38 MAPK enzyme, a serine/threonine kinase involved in cell cycle proliferation and cytokine secretion. These results indicate that mutolide may exert its anti-inflammatory effect via NF-κB inhibition. Oral administration of mutolide at 100 mg/kg showed significant inhibition of LPS-induced release of TNF-α from Balb/c mice in an acute model of inflammation. Our results highlight the anti-inflammatory properties of mutolide and suggest that further evaluation in a chronic model of inflammation is required to confirm the potential of mutolide as a druggable candidate for the treatment of inflammatory diseases. More... »

PAGES

706

References to SciGraph publications

  • 2006-07. Interleukin-6: a new therapeutic target in ARTHRITIS RESEARCH & THERAPY
  • 2011-06. Fungal endophytes: unique plant inhabitants with great promises in APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
  • 2007-12. Transcriptional profiling of the LPS induced NF-κB response in macrophages in BMC IMMUNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s40064-015-1493-6

    DOI

    http://dx.doi.org/10.1186/s40064-015-1493-6

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26618095


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